The relative importance of vascular, glomerular and tubular dynamics in the pathogenesis of toxin- and hemodynamically-related acute renal failure will be investigated using micropuncture, clearance, light and electron microscopic methods. The results of pathogenetic studies performed serially througout the course of disease will be used as the basis for preventative and treatment programs in this disorder. The initial portion of the study is to be devoted to the development of disease models in Munich Wistar and Sprague-Dawley rats that closely simulate the course of acute renal failure in man. Detailed functional and anatomic studies will be carried out in the pre-induction state and throughout the course of acute renal failure. Hemodynamics of individual surface glomeruli and peritubular vasculature will be investigated using servo-null pressure monitoring and micro-plasma protein analysis. Tubular function will be evaluated with pressure determinations and measurement of reabsorptive capacity using standard collection and microperfusion methods. Simultaneous measurements of whole kidney blood flow and glomerular filtration will also be performed. Light and electron microscopy will be performed on glomeruli and tubular segments during each period of study. Attempts will be made to identify and characterize obstructing tubular casts found in the early phase of post-ischemic acute renal failure. The studies should provide more complete understanding of the pathogenesis of acute renal failure and will provide physiologic data that will aid in the control of acute renal failure. The ability to detect a specific substance in the urine of high-risk ARF subjects may form the basis for early acute renal failure preventative therapy.